Chronic Rhinosinusitis with Nasal Polyps: A “Module-First” Review of Murine Models and Chemical Interventions

Chronic rhinosinusitis with nasal polyps (CRSwNP) comprises multiple molecular endotypes that only partly align with the clinical phenotype, which complicates target selection and interpretation of treatment effects. Human omics and biomarker studies define candidate pathways, but causal attribution of specific nodes to lesion formation and remodeling requires perturbable in vivo systems. Here, we present a “module-first” framework that links murine induction paradigms to epithelial–immune–stromal circuits and to a minimal, module-matched endpoint set for reproducible causal inference. We summarize commonly used CRSwNP-like protocols (allergen/protease ± SEB, aeroallergen + SEB, innate trigger-enriched paradigms, and modifier layers), emphasize operational pathology terminology (“polyp-like lesion” versus “true polyp”), and propose a uniform causal template for validated pathway modules (alarmins/IL-33–NF-κB, type 2/ILC2–eosinophil, IL-17A/neutrophil, Wnt/EMT remodeling, and JAK/STAT kinase convergence). Finally, we organize chemical and molecular interventions by leverage point and propose an ARRIVE-aligned Minimum Reporting Set to standardize model anchoring, target engagement, and cross-study comparability. This module-first roadmap is intended to accelerate mechanism-linked discovery and preclinical validation of tractable drug targets in CRSwNP. Importantly, this module-first roadmap is intended as a heuristic organizing principle rather than an exhaustive taxonomy, because pathway modules can overlap and shift dynamically across time and tissue compartments in vivo.